CyBeR Association in Relapsed/Refractory DLBCL

Diffuse Large B Cell Lymphoma Clinical Trial

— CyBeR-Lymph  

Official title:

Phase 2 Study of Cytarabine in Association With Bendamustine and Rituximab in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02758925
• Other study ID #: 2015-005837-37
• Status: Not yet recruiting
• Phase: Phase 2
• First received: April 14, 2016
• Last updated: May 3, 2016
• Start date: June 2016
• Est. completion date: December 2018

Study information

• Verified date: May 2016
• Source: University Hospital, Caen
• Contact: Emilie Reboursiere, MD
• Phone: +33231272140
• Email: reboursiere-e[@]chu-caen.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Forty percent of patients with diffuse large B cell lymphoma (DLBCL) have primary refractory or relapsed disease (R/R). For these fit patients, standard treatment in second line therapy is high dose therapy with autologous stem cell transplantation (ASCT). In 48% of DLBCL no ASCT is possible due to progressive disease. For these patients or ineligible to transplantation patients, salvage therapy is often rituximab-gemcitabine-oxaliplatine regimen with an overall response rate (ORR) about 50%.

Bendamustine in combination with rituximab, used as a single agent in the setting of R/R DLBCL patients, have shown an ORR of 62.7% and 45.8% with a good safety profile.

Bendamustine and cytarabine (BAC) showed high synergy in inducing cell death in mantle cell lymphoma and DLBCL cell lines. In a recent phase II study, the combination of cytarabine with Rituximab and Bendamustine (R-BAC) in patients with mantle cell lymphoma who were previously untreated, refractory or relapsed was evaluated.

The efficacy and safety of the R-BAC association will be evaluated in this phase II trial enrolling 78 patients with relapsed or refractory DLBCL.

Description:

Participants will received 6 cycles every 21 days with a follow-up period of 24 months.

CT-Scan after 3 cycles and at the end of the treatment will be used to assess treatment response, established with Cheson criteria in 1999.

Principal objective is to obtain an overall response rate of 60% (corresponding to an increased of 15% of the rituximab-gemcitabine-oxaliplatine regimen's overall response rate).

Secondaries objectives are to value toxicity, progression free survival and overall survival.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 78
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. patients from 18 to 75 years

2. Patient sharpened the social security system

3. Patients with relapsed or refractory diffuse large B cell lymphoma who received at least one prior line of immunochemotherapy unfit for intensive regimen therapy and autologous stem cell transplantation (ASCT) eligible patients to stem cell transplantation with failure of the salvage therapy patients with relapse after ASCT

4. Not previously treated with bendamustine

5. WHO performance status 0, 1 or 2

6. Adequate hematological function as defined by: leucocyte count = 3.0 109/L, platelet count = 75 109/L

7. Females of childbearing potential must agree to have a medically acceptable method of contraception from study treatment initiation until the end of treatment.

8. Signed informed consent.

Exclusion Criteria:

1. Person under guardianship or curatorship , or unable to understand the purpose of the study

2. Central nervous system or meningeal involvement

3. WHO performance status more than 2

4. Contraindication to any drug contained in the chemotherapy regimen

5. HIV disease, active hepatitis B or C

6. Any serious active disease or co-morbid medical condition

7. Any of the following laboratory abnormalities.

• Leucocyte count < 3.0 x 109/L

• Platelet count < 75 x 109/L

8. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

9. Pregnant or lactating females.

10. Prior history of malignancies, other than lymphoma, unless the patient has been free of the disease for = 3 years. Exceptions include the following:

• Basal cell carcinoma of the skin.

• Squamous cell carcinoma of the skin.

• Carcinoma in situ of the cervix.

• Carcinoma in situ of the breast.

• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).

11. renal impairment with an estimated (modified dietin renal disease; MDRD) creatinine clearance < 40 ml/min,

12. chronic liver disease or day-1 (AST/ALT )=2.5 upper limit of normal (ULN), total bilirubin=1.5 ULN,

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
375mg/m2 IV day 1
• Bendamustine
90mg/m2 IV day 1-2
• Cytarabine
1000mg/m2 or 750mg/m2 at day 2 if patients aged more than 70 years or toxicity grade 3/4

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

References & Publications (6)

Castegnaro S, Visco C, Chieregato K, Bernardi M, Albiero E, Zanon C, Madeo D, Rodeghiero F. Cytosine arabinoside potentiates the apoptotic effect of bendamustine on several B- and T-cell leukemia/lymphoma cells and cell lines. Leuk Lymphoma. 2012 Nov;53(11):2262-8. doi: 10.3109/10428194.2012.688200. Epub 2012 May 21. — View Citation

Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/rel — View Citation

Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. doi: 10.1200/JCO.2012.46.5203. Epub 2013 May 6. — View Citation

Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. doi: 10.1007/s00277-013-1879-x. Epub 2013 Aug 17. — View Citation

Visco C, Finotto S, Pomponi F, Sartori R, Laveder F, Trentin L, Paolini R, Di Bona E, Ruggeri M, Rodeghiero F. The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia. Am J Hematol. 2013 Apr;88(4):289-93. doi: 10.1002/ajh.23391. Epub 2013 Feb 28. — View Citation

Visco C, Finotto S, Zambello R, Paolini R, Menin A, Zanotti R, Zaja F, Semenzato G, Pizzolo G, D'Amore ES, Rodeghiero F. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013 Apr 10;31(11):1442-9. doi: 10.1200/JCO.2012.45.9842. Epub 2013 Feb 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	treatment response	established with 1999 Cheson criteria on CT-scan	up to 20 weeks (at the end of the treatment)	Yes
Secondary	overall survival		2 years	Yes
Secondary	progression free survival		2 years	Yes